Abstract: Molecular Profiling Core. Fibromyalgia (FM), irritable bowel syndrome (IBS), vulvar vestibulitis syndrome (WS), and episodic migraine (EM) are prevalent complex persistent pain conditions (CPPCs). CPPCs commonly aggregate as comorbid conditions and are characterized by a report of pain greater than expected upon physical examination. Because we do not understand the efiology of CPPCs, patients receive inadequate treatment and suffer severe physiologic, psychologic, and socioeconomic consequences. Recent studies suggest that CPPCs are mediated in large part by genefic variability which can produce functional consequences on the amount and/or activity of proteins, which regulate downstream signaling events that impact pain-relevant processes. However, little is known about the specific nature of the relationship between genotype and biologic activity and their relevance to clinical phenotype. Thus, the objective of the Molecular Profiling Core is to identify biologic mediators that contribute to CPPCs. This goal will be achieved through execution of three specific aims. In Aim I, FM, IBS, WS, and EM cases and pain free controls (N = 300 per group) will be genotyped using the Pain Research Panel developed by our investigative team to measure neariy 3,000 polymorphisms in 350 genes whose protein products are linked to biologic pathways that influence pain transmission, inflammatory response, or psychological state. In Aim II, changes in the expression of proteins corresponding to the 350 genes represented on the Pain Research Panel will be measured in plasma and leukocytes from cases and controls using custom protein microarray technology. Results of these studies will allow us to evaluate changes in protein expression patterns that direcfiy result from functional polymorphisms. Moreover, they will inform the design of studies associated with Aim III, which is to create a lymphoblast repository that will provide an in vivo system within which to model cell signaling processes based on genefic and protein analyses. Elucidating the pathophysiologic mechanisms that underlie CPPCs will facilitate the long-term goal of our program which is to provide more accurate subdiagnoses as well as individualized therapeutic regimens to individuals who suffer from these conditions.